1. Field of the Invention
The present disclosure in general relates to the treatment of nitric oxide (NO)-related diseases. More particularly, the present disclosure relates to two types of dinitrosyl iron complex (DNIC), and their uses as a NO-releasing reagent to treat NO-associated diseases and/or conditions.
2. Description of Related Art
Nitric oxide (NO, also known as nitrogen oxide or nitrogen monoxide) has a formula of ●NO, in which the dot ● represents an unpaired electron on the nitrogen atom. ●NO involves a variety of signal transduction pathways in vascular, immune, and neuronal system in multicellular organisms, whereas the nature of ●NO and the location where ●NO is generated dictate its physiological and pathological function. ●NO interacts with the heme center of soluble guanylate cyclase (sGC) to promote the conversion of GTP into cGMP and to activate cGMP-dependent vascular relaxation of blood vessels, cGMP/MAPK-dependent angiogenesis, and cGMP-dependent release of neurotransmitter. Bacterial ●NO modulates hsf-1/daf-16 related genes to enhance stress resistance and longevity in C. elegans. Through the interaction with nuclear receptor proteins UNF and E75, ●NO provides a concentration-dependent switching mechanism between the neuronal degenerative and regenerative states of axon. In Alexander disease, a serious degenerative neurological disorder, ●NO derived from glia triggers astrocyte-mediated neuronal degeneration and cell death.
Nitroxyl (NO−, also known as azanone) is a one-electron-reduction sibling of ●NO. Similar to ●NO, NO− has been shown to induce vasorelaxation via activating sGC. Besides, NO− also triggers a positive myocardial inotropic effect in the cardiovascular system that is independent from β-adrenergic signaling pathway, especially during a congestive heart failure condition. In addition to cardiovascular effects, it is reported that NO− exhibits an anti-cancer effect via inhibiting GAPDH activity.
Based on the biological functions, both ●NO and NO− donors have emerged as a promising agent to treat these ●NO and/or NO− related diseases. However, the current ●NO/NO− donors have some drawbacks, such as low activity, low solubility, poor specificity, short half-life, and adverse side-effect, that remain obstacles to clinical application. In view of the foregoing, there exists in the related art a need for a novel compound that has ●NO /NO− releasing activity and may be employed as a lead compound for preparing or manufacturing medicaments to treat ●NO/NO−-associated diseases and conditions.